论对合法的劳动收入的保护及其他

劳动收入有“受动型”和“自营型”两类 ,它们分别处于劳动法律关系和一般民事法律关系之中 ,判别劳动行为合法性有劳动主体资格和劳动行为方式及劳动行为后果的合法 ,合法行为所得的劳动收入方得到法律保护 。

New lead discovery for novel M_1 agonists:pharmacophore model based on DISCO computation and virtual screening

To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons （DISCO） method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds （ACD-SC） to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists.

Cumulus-specific genes are transcriptionally silent following somatic cell nuclear transfer in a mouse model

This study investigated whether four cumulus-specific genes: follicular stimulating hormone receptor (FSHr), hyaluronan synthase 2 (Has2), prostaglandin synthase 2 (Ptgs2) and steroidogenic acute regulator protein (Star), were correctly reprogrammed to be transcriptionally silent following somatic cell nuclear transfer (SCNT) in a murine model. Cumulus cells of C57×CBA F1 female mouse were injected into enucleated oocytes, followed by activation in 10 μmol/L strontium chloride for 5 h and subsequent in vitro culture up to the blastocyst stage. Expression of cumulus-specific genes in SCNT-derived embryos at 2-cell, 4-cell and day 4.5 blastocyst stages was compared with corresponding in vivo fertilized embryos by real-time PCR. It was demonstrated that immediately after the first cell cycle, SCNT-derived 2-cell stage embryos did not express all four cumulus-specific genes, which continually remained silent at the 4-cell and blastocyst stages. It is therefore concluded that all four cumulus-specific genes were correctly reprogrammed to be silent following nuclear transfer with cumulus donor cells in the mouse model. This would imply that the poor preimplantation developmental competence of SCNT embryos derived from cumulus cells is due to incomplete reprogramming of other embryonic genes, rather than cumulus-specific genes.

EFFECTS OF β-ENDORPHIN ON PHYTOHEMAGGLUTININ-INDUCED LYMPHOCYTE PROLIFERATION AND MOUSE PLAQUE-FORMING CELL RESPONSE VIA AN OPIOID RECEPTOR MECHANISM

The effects of opioid peptides on iminune responses were investigated. It was found that β-endorphin (β-END) can depress proliferative responses to PHA in rat splenocytes but enhance those in mice, and it could also inhibit the plaque-forming cell (PFC) response to sheep red blood cells when mouse splenocytes immunized in vivo were cultured in vitro with the peptide. The peptide antagonist naloxone was able to reverse β-END suppression of the PFC response. The data indicate that β-END suppresses antibody production or secretion via a specific opioidreceptor-mediated mechanism.

Empirical research on impacted factor of farmer＇s willingness for purchasing information Based on the survey data of Hebei province

Farmer＇s willingness for purchasing information, an important factor of farmer＇s information demand, was analyzed by logit model, according to the survey data of 535 farmers from eleven cities in Hebei province. The result showed that 6 factors had a significant influence on it, that is, education of farmers, per capita income of farmers, the affordability of information risk, the proportion of agricultural labor households, the type of agricultural production and the rural information service stations. On the basis of these, the related policy recommendations were proposed.

Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome

AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.

Advancements in glucagon-like peptide-1 receptor agonist therapy for type 2 diabetes

Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglycemic effects,and metabolic advantages.Their primary mechanisms of action encompass promoting insulin release,inhibiting glucagon secretion,bolstering pancreatic islet cell function,curbing appetite,and slowing gastric emptying.This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs.Notably,these agents have demonstrated marked improvements in glycemic control,significant weight reduction,and substantial cardiovascular and renal protection.Nonetheless,certain adverse effects of GLP-1RAs,such as pancreatitis and intestinal obstruction,have been reported,warranting vigilant monitoring by healthcare professionals.In sum,GLP-1RAs hold significant promise in the management of type 2 diabetes,offering notable cardiovascular and renal advantages.

Three-dimensional common-feature hypotheses for Toll-like receptor 7 agonists

Toll-like receptor 7 （TLR7）, the best known TLRs, has been demonstrated to be useful in fighting against infectious disease. In our study, three-dimensional （3D） pharmacophore models were constructed from a set of 5 TLR7 agonists. Among the 10 common-featured models generated by program Discovery Studio/HipHop, a hypothesis （Hypo2） including one hydrogen-bond donor （D）, one hydrogen-bond acceptor （A）, and two hydrophobic （H） features was considered to be important in evaluating the ligands with TLR7 agonistic activity. The obtained pharmacophore model was further validated using a set of test molecules and the Catalyst TLR7-agonist-subset database. Hypo2 has been shown to identify a range of highly potent TLR7 agonists. Finally, the obtained pharmacophore was further validated using docking studies. Taken together, this model can be utilized as a guide for future studies to design the structurally novel TLR7 agonists.

Pharmacophore identification and validation for human nAChR α7 agonists

Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher＇s Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics.

Pharmacodynamic model of dopamine D1 receptor agonists in the treatment of breast cancer lung metastasis

Previous study has shown that dopamine D1 receptor(D1DR)agonists,fenoldopam(FEN)and l-stepholidine(l-SPD),have inhibitory effects on breast cancer lung metastasis.To quantitatively describe and predict the pharmacodynamic(PD)properties of FEN and l-SPD and to explore the PD model structure of cancer metastasis treating drugs,we used the data of lung metastasis in 4T1 breast cancer mice under the treatment of either FEN or l-SPD,and established a PD model.The PD model assumed an exponential growth for both primary tumor and metastasis.The primary tumor emitted cells to form metastases,and the cell emitting rate was proportional to power form of the primary tumor weight.The total number of lung metastasis was set as the target value.D1DR agonists inhibited metastasis by inhibiting cell emitting rate instead of the growth rate of primary tumor or metastasis.The model results showed that the decrease in the number of lung metastases was roughly proportional to the square of the drug dose.The values of PD coefficient reflected the inhibitory ability of the drugs,and that of l-SPD(0.274 kg/mg)was greater than that of FEN(0.0393 kg/mg).This PD model can quantitatively describe the effects of FEN and l-SPD on the progression of lung metastasis in 4T1 primary breast cancer mice and can predict the time course of drug efficacy at multiple doses,providing a reference for PD model structure of other drugs for cancer metastasis indication.

Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor(GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB(NF-κB), p38 mitogen-activated protein kinase(P38 MAPK) and activator protein-1(AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.

Changes of metabotropic glutamate receptor subtype 1a in diffuse brain injury with secondary brain insults and the effects of 2-methyl-4-carboxyphenylglycine

Objective: To observe the changes of metabotropic glutamate receptor 1a in rat brain in a rodent model of diffuse head injury with secondary insults and the effects of 2 methyl 4 carboxyphenylglycine (MCPG). Methods: Based on Marmarous rodent model of diffuse brain injury (DBI), hypotension was made by blood withdrawal as secondary brain insults (SBI). 105 male SD rats were randomized into A and B groups. The changes of mGluR 1a in cerebral cortex were studied by immunohistochemistry and the effect of MCPG by HE. Each group was divided into different subgroups at different time after injury. Results: Compared with that of sham group, the number of mGluR 1a positive neuron increased by 12.9±3.2 (P< 0.05 ) 1 day after injury in the injured cerebral cortex in DBI group. However, in DBI and SBI group there was a more significant increase in the number of mGluR 1a positive neuron at 4 hours after injury ( 15.6±3.0 , P< 0.05 )and then the number of mGluR 1a positive neuron gradually decreased. Administration of MCPG reduced total cortical necrotic neurons counts on the 7th day after injury ( 5.21±2.52 , P< 0.05 ). Conclusions: Brain injury can increase the gene expression of mGluR 1a and the role of mGluR 1a may be a key factor in the aggravation of head injury with SBI, and that MCPG may have therapeutic potential in head injury.

Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease

Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.

The development and application of peroxisome proliferator-activated receptor(PPAR) modulator

The peroxisome proliferator-activated receptors （PPARs）, PPARt,, PPARβ/δ and PPARy, are ligand-activated transcriptional factors, which belong to the nuclear receptor super family and play crucial roles in glucose and lipid metabolism. Based on the impressive advantages ofPPAR agonists （like TZD and fibrate compounds） in the treatment of metabolic syndrome and type 2 diebetes, PPAR modulators have doubtlessly grabbed much more attention. However, serious clinical adverse effects, especially for PPARy agonists, hinder the development of PPAR agonist, Therefore, the selectivity and safety would be the key points and have been taken into the consideration for novel generation PPAR agonist research, and then several dual- or pan-PPAR modulators have emerged. Furthermore, experimental study indicates that partial agonists can neutralize the side effect and achieve modest therapeutic effect. This review summaries structural features of PPAR receptors, illustrates the method of PPAR modulator design, then lists and analyzes recent dual- and nan- agonists

Overweight and obesity versus concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 in plasma of patients with lower limb chronic ischemia

Objective： Being overweight or obese comprises a significant risk factor for atherosclerosis. Fat tissue also generates factors stimulating angiogenesis, the process by which new blood vessels form. The purpose of this paper is to assess concentrations of the vascular endothelial growth factor A （VEGF-A） and its soluble type-1 and type-2 re- ceptors （sVEGFR-1 and sVEGFR-2） in plasma of patients with peripheral arterial disease （PAD） depending on the level of nutrition according to body mass index （BMI）. Methods： The study group included patients suffering from symptomatic PAD （n=46） in Fontaine classes Ila-lV without any history of neoplastic disease and who have a normal BMI （n=15）, are overweight （n=21） or are obese （n=10）. The control group （n=30） consisted of healthy non-smoking volunteers who were neither overweight nor obese. Venous blood plasma samples were collected from both groups at rest in the morning to determine plasma concentrations of VEGF-A, sVEGFR-1, and sVEGFR-2 using the enzyme- linked immunosorbent assay （ELISA） method. Results： The group of patients with PAD co-existent with being over- weight or obese tended to have higher mean concentration levels of VEGF-A and sVEGFR-2 when compared with patients suffering from PAD with normal BMIo A statistically significant positive correlation was obtained between BMI and average plasma concentrations of sVEGFR-2 （R=0.37, P=-0.0103）. However, no significant correlation was no- ticed between BMI and VEGF-A or sVEGFR-1 concentrations. Conclusions： A positive correlation determined be- tween the level of antiangiogenic factor and BMI value may be indicative of the linearly growing prevalence of some antiangiogenic factors in patients with metabolic disorders, which may be one of numerous factors contributing to incomplete efficiency of collateral circulation development in patients with PAD.